For years 12-17 of this program project we plan to continue to focus on mechanisms of latency and oncogenesis of the Epstein-Barr Virus, supplemented by studies of other viruses that produce latent infections, selected because they offer advantages for and reinforce the central investigational thrust. The main lines of research deal with EBV gene functions that may be important in producing cell transformation, mechanisms of episomal maintenance in latent EBV infection, regulation of EBV gene expression, especially those that may govern latency, oncogenic functions and virus reactivation.and interrelated studies of vitally encoded DNA polymerase with emphasis on expression and mutagenesis. This is a deliberately refashioned program project, taking advantage of new strengths and resources of the Lineberger Cancer Research Center and designed to be a cohesive interdisciplinary program. Participants who are PIs or Co-PIs are faculty members in six departments and interdisciplinary programs: Microbiology, Biochemistry, Medicine, Genetics, Molecular Biology and Cancer. New PIs in the program are: Dr. Nancy Raab-Traub, Dr. Shannon Kenney, and Dr. Ron swanstrom. The projects are as follows: Nancy Raab-Traub, Ph.D.: "Oncogenic potential of EBV latency and transforming genes"; Shannon Kenney, M.D.: "Negative regulation of EBV gene expression"; Jung_Chung Lin, Ph.D. and Joseph S. Pagano, M.D. : "Epstein-Barr Virus DNS-binding proteins"; Steven Bachenheimer, Ph.D.: "DNS-protein interactions in HSV and EBV DNA polymerase: expression and regulation"; Eng- Shang Huang, Ph.D.: "Human cytomegalovirus-specific DNA polymerase"; Ronald Swanstrom, Ph.D.: "Hiv 2 and SIV pol genes". The core components consist of Tissue Culture, Electron Microscopy (Jack Griffith, Ph.D.) and Virus Containment. This assemblage of faculty and projects, building on the past accomplishments of the VPP, is expected to yield important new information and insights bearing on central issues of the molecular pathobiology of EBV.